Cloning, function, and localization of human, canine, and drosophila ZIP10 (SLC39A10), a Zn²⁺ transporter

Zinc (Zn²⁺) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn²⁺ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn²⁺ is nephrotoxic. As for other ions and solutes, Zn²⁺ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn²⁺ import. Renal regulation of Zn²⁺ is of particular interest in light of growing evidence that Zn²⁺ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn²⁺, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn²⁺ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn²⁺ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn²⁺ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10.